Abstract

?9-Tetrahydrocannabinol (?9-THC), the primary psychoactive constituent of marijuana (Cannabis sativa), is known to bind to two cannabinoid receptors: CB1 receptors, located primarily in the brain, and CB2 receptors, located primarily in the periphery. Recent research has suggested that other cannabinoids, including anandamide and WIN 55,212-2, may also act at novel non-CB1, non-CB2 cannabinoid receptor(s). Anandamide produces a number of in vivo pharmacological effects in CB1 knockout mice that are not produced by ?9-THC and cannot be explained by anandamide's rapid metabolism. In addition, in vitro anandamide and WIN 55,212-2 stimulate [35S]GTP?S binding in both CB1 knockout and wildtype mice while ?9-THC stimulates this binding only in wildtype mice. Although anandamide and vanilloid agonists share pharmacological effects, anandamide's actions in CB1 knockout mice do not appear to be mediated by vanilloid VR1 receptors. While not yet conclusive, these results suggest the possibility of additional cannabinoid receptors in the brain and periphery.